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Immunotherapy Aug 2021
Topics: Animals; Glioblastoma; Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Tumor-Associated Macrophages
PubMed: 34078139
DOI: 10.2217/imt-2021-0054 -
Cancer Cell Jun 2020In this issue of Cancer Cell, Gurusamy et al. use a CRISPR-Cas9 screening approach to demonstrate that deletion of p38 increases multiple phenotypic qualities of...
In this issue of Cancer Cell, Gurusamy et al. use a CRISPR-Cas9 screening approach to demonstrate that deletion of p38 increases multiple phenotypic qualities of effective anti-tumor T cells. Preconditioning T cells with a p38 inhibitor enhances anti-tumor efficacy of adoptive immunotherapy.
Topics: CRISPR-Cas Systems; Gene Editing; Immunotherapy, Adoptive; Phenotype; T-Lymphocytes
PubMed: 32516586
DOI: 10.1016/j.ccell.2020.05.012 -
The Western Journal of Emergency... Apr 2020Cancer therapies have undergone several recent advancements. Current cancer treatments include immune-based therapies comprised of checkpoint inhibitors, and adoptive... (Review)
Review
Cancer therapies have undergone several recent advancements. Current cancer treatments include immune-based therapies comprised of checkpoint inhibitors, and adoptive immunotherapy; each treatment has the potential for complications that differ from chemotherapy and radiation. This review evaluates immune-based therapies and their complications for emergency clinicians. Therapy complications include immune-related adverse events (irAE), cytokine release syndrome (CRS), autoimmune toxicity, and chimeric antigen receptor (CAR) T-cell-related encephalopathy syndrome (CRES). Immune-related adverse events are most commonly encountered with checkpoint inhibitors and include dermatologic complications, pneumonitis, colitis/diarrhea, hepatitis, and endocrinopathies. Less common irAEs include nephritis, myocardial injury, neurologic toxicity, ocular diseases, and musculoskeletal complications. CRS and CRES are more commonly associated with CAR T-cell therapy. CRS commonly presents with flu-like illness and symptoms resembling sepsis, but severe myocardial and pulmonary disease may occur. Critically ill patients require resuscitation, broad-spectrum antibiotics, and hematology/oncology consultation.
Topics: Antineoplastic Agents, Immunological; Emergency Medical Services; Humans; Immune System Diseases; Immunotherapy, Adoptive; Medical Oncology; Neoplasms
PubMed: 32421502
DOI: 10.5811/westjem.2020.1.45898 -
Immunotherapy Jan 2012
Topics: Animals; Autophagy; Gene Transfer Techniques; Humans; Immunotherapy, Adoptive; Neoplasms; T-Lymphocytes; Tumor Microenvironment
PubMed: 22149992
DOI: 10.2217/imt.11.144 -
Cell Biology and Toxicology Dec 2018
Topics: Animals; CD8-Positive T-Lymphocytes; Hematopoietic Stem Cells; Humans; Immunotherapy, Adoptive
PubMed: 30094641
DOI: 10.1007/s10565-018-9442-0 -
British Journal of Haematology Aug 1998
Review
Topics: Acute Disease; Chronic Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunization; Immunotherapy, Adoptive; Leukemia; Leukocyte Transfusion; Recurrence; Transplantation, Homologous
PubMed: 9722287
DOI: 10.1046/j.1365-2141.1998.00830.x -
Clinical Trials (London, England) Apr 2020Dose feasibility is a challenge that may arise in the development of adoptive T cell therapies for cancer. In early-phase clinical trials, dose is quantified either by a...
BACKGROUND/AIMS
Dose feasibility is a challenge that may arise in the development of adoptive T cell therapies for cancer. In early-phase clinical trials, dose is quantified either by a fixed or per unit body weight number of cells infused. It may not be feasible, however, to administer a patient's assigned dose due to an insufficient number of cells harvested or functional heterogeneity of the product. The study objective becomes to identify the maximum tolerated dose with high feasibility of being administered. This article describes a new dose-finding method that adaptively accounts for safety and feasibility endpoints in guiding dose allocation.
METHODS
We propose an adaptive dose-finding method that integrates accumulating feasibility and safety data to select doses for participant cohorts in early-phase trials examining adoptive cell immunotherapy. We sequentially model the probability of dose-limiting toxicity and the probability of feasibility using independent beta-binomial models. The probability model for toxicity borrows information across all dose levels using isotonic regression, allowing participants infused at a lower dose than his or her planned dose to contribute safety data to the dose-finding algorithm. We applied the proposed methodology in a single simulated trial and evaluated its operating characteristics through extensive simulation studies.
RESULTS
In simulations conducted for a phase I study of adoptive immunotherapy for newly diagnosed glioblastoma, the proposed method demonstrates the ability to identify accurately the feasible maximum tolerated doses and to treat participants at and around these doses. Over 10 hypothesized scenarios studied, the percentage of correctly selecting the true feasible and maximum tolerated dose ranged from 50% to 90% with sample sizes averaging between 21 and 24 participants. A comparison to the only known existing method accounting for safety and feasibility yields competitive performance.
CONCLUSION
We have developed a new practical adaptive dose-finding method to assess feasibility in early-phase adoptive cell therapy trials. A design that incorporates feasibility, as a function of the quantity and quality of the product manufactured, in addition to safety will have an impact on the recommended phase II doses in studies that evaluate patient outcomes.
Topics: Algorithms; Clinical Trials, Phase I as Topic; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Endpoint Determination; Feasibility Studies; Humans; Immunotherapy, Adoptive; Maximum Tolerated Dose; Models, Statistical; Neoplasms; Research Design
PubMed: 31856602
DOI: 10.1177/1740774519890145 -
Cancer Control : Journal of the Moffitt... 2024Chimeric antigen receptor T cell therapy is used to treat hematological malignancies which are refractory to standard therapy. It is a form of immunotherapy in which a... (Review)
Review
Chimeric antigen receptor T cell therapy is used to treat hematological malignancies which are refractory to standard therapy. It is a form of immunotherapy in which a patient's T cells are programmed to act against tumor cells. We discuss the process of manufacturing CAR-T cells, the common side effects of therapy, and the recent emerging risk of T-cell malignancies after treatment.
Topics: Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; T-Lymphocytes; Hematologic Neoplasms; Receptors, Antigen, T-Cell
PubMed: 38910268
DOI: 10.1177/10732748241263713 -
ILAR Journal 2014Immunotherapy is not a new concept for veterinary medicine; however, adoptive T cell therapy is a new area of research in humans and canines alike. In humans, T cell... (Review)
Review
Immunotherapy is not a new concept for veterinary medicine; however, adoptive T cell therapy is a new area of research in humans and canines alike. In humans, T cell therapy has been used against many different tumor histologies, including lymphoma, melanoma, and colon cancer. Although in dogs this approach has currently only been applied to lymphoma, other tumor types are under investigation. There are many different strategies used to take advantage of cell-mediated antitumor properties of T cells. This review will discuss many of the current strategies used in both humans and canines in regards to adoptive T cell therapy.
Topics: Animals; Disease Models, Animal; Dog Diseases; Dogs; Immunotherapy, Adoptive; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Pets; Protein Engineering; Receptors, Antigen; T-Lymphocytes
PubMed: 24936037
DOI: 10.1093/ilar/ilu020 -
BMJ (Clinical Research Ed.) May 2024In addition to conventional chemoradiation and targeted cancer therapy, the use of immune based therapies, specifically immune checkpoint inhibitors (ICIs) and chimeric... (Review)
Review
In addition to conventional chemoradiation and targeted cancer therapy, the use of immune based therapies, specifically immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T cell therapy (CAR-T), has increased exponentially across a wide spectrum of cancers. This has been paralleled by recognition of off-target immune related adverse events that can affect almost any organ system including the cardiovascular system. The use of ICIs has been associated with myocarditis, a less common but highly fatal adverse effect, pericarditis and pericardial effusions, vasculitis, thromboembolism, and potentially accelerated atherosclerosis. CAR-T resulting in a systemic cytokine release syndrome has been associated with myriad cardiovascular consequences including arrhythmias, myocardial infarction, and heart failure. This review summarizes the current state of knowledge regarding adverse cardiovascular effects associated with ICIs and CAR-T.
Topics: Humans; Neoplasms; Immune Checkpoint Inhibitors; Immunotherapy, Adoptive; Cardiovascular Diseases; Cardiotoxicity; Myocarditis; Cytokine Release Syndrome; Pericarditis
PubMed: 38749554
DOI: 10.1136/bmj-2023-075859